The focus of this proposal is how fatigue affects cognitive performance. While the specific pathogenic mechanisms remain unclear, fatigue is likely due to a depletion of energy sources resulting from metabolic and/or immunologic factors. Successful programs for prevention and rehabilitation first require the identification of fatigue. Fatigue may be defined as "the inability to maintain expected power output" and is measured by a decline in performance over time. This definition has been successfully applied to the measurement of physical aspects of fatigue(e.g. decrements in motor force over time). We propose that cognitive fatigue should also be identified with this definition, and measured by declines in cognitive functioning over time. Based on the definition of fatigue as an inability to maintain expected power output over time, we have developed a model of cognitive fatigue. Addressing the limitations of previous approaches, our model measures several areas of cognitive functioning at two time-points, separated by a cognitively effortful task. Using our model, we propose to define cognitive fatigue in two conditions in which cognitive dysfunction is a prominent feature: subjects with MS and healthy sleep-deprived subjects.